Association

BACKGROUND

Six-pyruvoyl-tetrahydrobiopterin synthase (6-PTPS) deficiency is an inherited metabolic disorder which results in tetrahydrobiopterin (BH4) deficiency causing hyperphenylalaninemia.

This study aimed to describe the clinical, biochemical, and radiologic profiles, and neurologic and developmental outcomes of patients diagnosed with 6-pyruvoyl tetrahydrobiopterin (PTPS) deficiency through newborn screening and confirmed by BH4 loading test, pterin analysis, and gene sequencing who were following-up with the metabolic team.

The research was a single-center descriptive case series study design that was done at the Philippine General Hospital, a tertiary government hospital. The clinical, biochemical, radiologic profiles and neurodevelopmental evaluation of each patient were described.

Nine patients from 1 year 2 months to 14 years 5 months of age were enrolled in the study. Clinical manifestations before treatment were hypotonia, poor suck, and seizure. The most common clinical manifestation even after treatment initiation was seizure. The mean phenylalanine level on newborn screening was 990.68 umol/L, but after treatment was started, mean levels ranged from 75.69 to 385.09 umol/L. Two of the patients had focal atrophy of the posterior lobe on brain imaging. Pathogenic variants on molecular analysis were all missense, with two predominant variants, c.155A>G and c.58T>C. Eight of the nine patients had varying degrees of developmental delay or intellectual disability, while the remaining patient had signs of a learning disorder.

Newborn screening has played a crucial role in the early identification and management of patients with hyperphenylalaninemia due to 6-PTPS deficiency. Confirmation of diagnosis through determination of DHPR activity, urine pterins and/or molecular analysis is necessary for appropriate management. However, despite early initiation of treatment, neurodevelopmental findings of patients with 6-PTPS deficiency were still unsatisfactory.

Background: Six-pyruvoyl-tetrahydrobiopterin synthase (6-PTPS) deficiency is an inherited metabolic disorder which results in tetrahydrobiopterin (BH4) deficiency causing hyperphenylalaninemia. Objective: This study aimed to describe the clinical, biochemical, and radiologic profiles, and neurologic and developmental outcomes of patients diagnosed with 6-pyruvoyl tetrahydrobiopterin (PTPS) deficiency through newborn screening and confirmed by BH4 loading test, pterin analysis, and gene sequencing who were following-up with the metabolic team. Methods: The research was a single-center descriptive case series study design that was done at the Philippine General Hospital, a tertiary government hospital. The clinical, biochemical, radiologic profiles and neurodevelopmental evaluation of each patient were described. Results: Nine patients from 1 year 2 months to 14 years 5 months of age were enrolled in the study. Clinical manifestations before treatment were hypotonia, poor suck, and seizure. The most common clinical manifestation even after treatment initiation was seizure. The mean phenylalanine level on newborn screening was 990.68 umol/L, but after treatment was started, mean levels ranged from 75.69 to 385.09 umol/L. Two of the patients had focal atrophy of the posterior lobe on brain imaging. Pathogenic variants on molecular analysis were all missense, with two predominant variants, c.155A>G and c.58T>C. Eight of the nine patients had varying degrees of developmental delay or intellectual disability, while the remaining patient had signs of a learning disorder. Conclusion Newborn screening has played a crucial role in the early identification and management of patients with hyperphenylalaninemia due to 6-PTPS deficiency. Confirmation of diagnosis through determination of DHPR activity, urine pterins and/or molecular analysis is necessary for appropriate management. However, despite early initiation of treatment, neurodevelopmental findings of patients with 6-PTPS deficiency were still unsatisfactory.

BACKGROUND

Newborns screened positive for Galactosemia through Expanded Newborn Screening (ENBS) with borderline levels undergo lactose challenge that requires interruption of breastfeeding temporarily then shifting to soy-based formula.

To determine the percentage of Classical Galactosemia (CGal), Non-classical Galactosemia (NCGal), probable mild variant form, and negative Galactosemia among newborns screened positive for Galactosemia who underwent lactose challenge.

This is a retrospective study. NBS records were reviewed and data were collected from January 2015 to December 2020.

Out of the 117 newborns screened positive for Galactosemia, 58 underwent lactose challenge. Majority were male, term with a birth weight of 2500-4000g and received a final disposition in 4-6 months. Fifteen patients underwent 1-week lactose challenge wherein six reached a resolution on first challenge. Majority, 35 (60.3%) were negative for Galactosemia, six (10.3%) probable mild variant Galactosemia, three (5.2%) NCGal, and no CGal were observed. Fourteen suspected cases (24.1%) are pending final disposition.

This study describes the demographics of newborns flagged for Galactosemia who underwent lactose challenge. A 1-week lactose challenge may be recommended to further detect patients who are negative for Galactosemia.

Background: Telegenetics has been a very useful platform to continue the different services offered by the clinical genetics team especially during the COVID-19 pandemic, when this mode of care had been maximized. Objective: This paper aimed to present the process of telegenetics in a tertiary hospital and the feedback for this service through patient satisfaction surveys. Methods: Telegenetics consultation is divided into three phases: pre-consultation, consultation, and post-consultation. Patient satisfaction in the delivery of genetics services were obtained through a survey answered by patients/caregivers after telegenetics consultation. Ratings of patient satisfaction on telegenetics consultation during the pandemic (September 2020 to February 2021) were compared from that of face-to-face consultations before the pandemic (September 2019 to February 2020). Results: In 2020, there were a total of 1,228 consultations made via telegenetics. Of which, 319 consultations were for the metabolic service, 138 for dysmorphology, 207 for genetic counseling, and 564 for dietary counseling. New patients comprised 13.84% of the consultations and 86.16% were from follow-up patients. In 2021, there were a total of 3,124 consultations made via telegenetics. Of which, 617 consultations were for the metabolic service, 688 for dysmorphology, 961 for genetic counseling, and 858 for dietary counseling. New patients comprised 12.93% of the consultations and 87.07% were from follow-up patients. Over a period of 6 months, pre-pandemic (face-to-face consultation) and pandemic (telegenetics) patient satisfaction survey results showed no significant difference on the results for both new patient consultations and follow-up patient consultations that is a standard satisfactory rating of at least 3 (satisfactory) on customer satisfaction by more than 70% of the respondents. Conclusion Patient satisfaction ratings on the utility of telegenetics was comparable to that of face-to-face consultations. Its use has shown benefits like cost-effectiveness, time efficiency, improved accessibility, and psychological benefits as some patients fear a hospital setting during the pandemic. It also has limitations like possible technical difficulties during consultations and limited opportunity for physical examination, establishing rapport, and exploring psychosocial issues. Hence it is important to consider the possibility of a telegenetics consultation as an alternative to a face-to-face consultation.
Patient Satisfaction

Schinzel-Giedion syndrome is a rare condition characterized by dysmorphic features, neurologic features, urogenital abnormalities, and radiographic changes. The etiology has been traced to mutations in the SETBP1 gene. We report a Filipino patient with features suggestive of Schinzel-Giedion Syndrome and the first to be confirmed through molecular testing.

Berardinelli-Seip Congenital Lipodystrophy (BSCL) is an autosomal recessive inborn error of the common pathway of acylglycerol and phospholipid synthesis. Patients with this condition present with generalized lipoatrophy, hepatomegaly, acromegalic features, hypertrichosis, and developmental delay. But on workup, they may also be discovered to have hypertriglyceridemia with or without hypercholesterolemia and insulin resistance. A high index of suspicion is required for diagnosis which may have implications in management. Here we present a 5-year old male with clinical features of BSCL. BSCL2 gene sequencing done showed a homozygous c.782dupG, p.(Ile262Hisfs*12) sequence alteration, classified as pathogenic, hence, confirming the diagnosis of BSCL. This is the first reported case in the Philippines.

Key Words: Berardinelli-Seip Congenital Lipodsytrophy, insulin resistance

We present a case of a 13-year-old Filipino patient with ambiguous genitalia, randomly assigned as female at birth and was subsequently reared as such. Starting at 10 years of age, secondary male sexual characteristics emerged. However, medical consultation was sought only when the patient developed a gradually enlarging and painful abdominal mass. After cytogenetic studies, we are able to identify the case as Disorder of Sex Development, 45,X/46,X,der(Y) mosaicism, mixed gonadal dysgenesis. Further imaging, laparotomy and histopathology, revealed that the abdomino-pelvic mass was from the right ovary, composed of immature teratoma. Ductus deferens and epididymis were also identified within the right ovary. At the time of presentation, the patient was already experiencing gender dysphoria. This report not only highlights the wide spectrum of phenotypes in mixed gonadal dysgenesis, but also stresses the importance of proper gender assignment during the newborn period in patients with disorders of sex development.

Key Words: disorder of sexual development, ambiguous genitalia, mixed gonadal dysgenesis, mosaicism, 45,X/46,X,der(Y) karyotype, immature teratoma, gender dysphoria

Asymmetric overgrowth syndromes are a diverse group of diseases with overlapping features including asymmetric overgrowth of a body part, vascular malformations, lipomatosis, and epidermal nevus. Three important considerations when presented with these features are Proteus syndrome, CLOVES (Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Skeletal anomalies) syndrome and SOLAMEN (Segmental Overgrowth, Lipomatosis, Arteriovenous Malformation, Epidermal Nevus) syndrome. This paper aimed to present a rare case of asymmetric overgrowth syndrome. A 3-year-old child with asymmetric overgrowth of the right upper and lower extremities was seen at the clinic. He also had epidermal nevus, lipomatosis, skeletal abnormalities, and vascular malformation. The history showed the presence of segmental proportionate overgrowth with soft tissue hypertrophy and ballooning effect based specifically on the location, timing, and progression of overgrowth. On physical examination, macrocephaly was also noted. Based on these features, the diagnosis of SOLAMEN syndrome was made. This is the first reported case of SOLAMEN syndrome in the Philippines. The importance of a careful and thorough history and physical examination cannot be overemphasized. A multidisciplinary approach in management with appropriate referral to subspecialists and early monitoring for possible malignancies are needed.
Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi

Objective: The study is a retrospective review which provides preliminary data on the correlation between biochemical profiles and initial clinical manifestation of patients diagnosed to have argininosuccinate synthetase deficiency (ASSD) and argininosuccinate lyase deficiency (ASLD) detected by expanded newborn screening (ENBS). Methods: This is a study of five distal UCD patients initially detected by elevated citrulline on ENBS. Medical charts of the patients were reviewed. The initial clinical manifestations of the patients were correlated with results of biochemical tests. Results: There were four cases of ASLD and one case of ASSD reviewed in this study. All cases of ASLD were confirmed by the presence of argininosuccinic acid (ASA) in the urine metabolic screen (UMS). The plasma citrulline level of the ASSD patient is significantly elevated as compared to the ASLD patients (2,690 µmol/L; NV: 10-45 µmol/L). The ASSD patient and one ASLD patient were symptomatic within the first six days of life. Both presented with significantly elevated plasma ammonia, citrulline and glutamine levels. Three ASLD patients were asymptomatic on initial screening. Conclusion ENBS has shown importance in the early detection and management of ASSD and ASLD. Early initiation of management may prevent hyperammonemic crises. Long term outcome studies are needed to look into the correlation of neurodevelopmental outcome with lifelong accumulation of citrulline and glutamine in ASSD and ASA in ASLD.
Citrullinemia ; Argininosuccinic Aciduria ; Argininosuccinic Acid