Genetics, Medical

Glycogen storage disease (GSD) type IXa, due to a deficiency of hepatic phosphorylase b kinase, results in liver enlargement, growth retardation and fasting ketosis. Many are asymptomatic and do not require treatment. This is the first documented GSD IXa in a Filipino boy evaluated for short stature.
Glycogen Storage Disease ; Hepatomegaly

Background: Disorders of Sex Development (DSD) are conditions that arise from an abnormality of the typical structural, chromosomal and/or gonadal characteristics of sex development. The incidence of DSD is not well established in the Philippines and there is no published local data. The complex nature of DSD requires streamlined multidisciplinary team management and guidelines from the 2006 Consensus meeting have become the standard of care for patients. Objective: The study describes the phenotype, biochemical, diagnostic and management profiles of patients with Disorders of Sex Development (DSD) excluding congenital adrenal hyperplasia (CAH) at the Philippine General Hospital, a tertiary care medical facility. Methods: Medical records of patients with DSD seen at the Division of Clinical Genetics from 2012-2016 were reviewed. Histories, demographic profiles, clinical features, co-existing health conditions, laboratory, imaging results, and interventions (medical or surgical) were recorded into a clinical report form. Results: Fifty-five (55) patient charts were included of all the patients with DSD listed in the registry. The neonatal period was the most common time DSD was first noted (69.09%). Most (58.18%) were assigned the male sex. The most common genital anomalies were hypospadias (45.45%), cryptorchidism (21.82%), and micropenis (12.73%). Associated health conditions included multiple congenital anomalies (32.73%), genitourinary with or without gastrointestinal anomalies (16.36%) and dysmorphic features (12.73%). Among 28 patients with karyotypes, there were 12 patients with sex chromosome DSD; two 46, XX DSD and fourteen 46, XY DSD. Four patients were prescribed hydrocortisone, three of whom had higher levels of 17-OH progesterone beyond cut-off level (2 preterm, 1 full term) while 1 full term presented with genital ambiguity; one case of Klinefelter syndrome was given testosterone replacement. Ten patients underwent corrective surgery for urogenital anomalies. Repair of hypospadias was the most common procedure. Repairs of associated anomalies (neurologic, cardiac, gastrointestinal, genitourinary) were done in 6 patients. Conclusion Complete history, meticulous physical examination and comprehensive investigations are important for the confirmation of DSDs. Uniform classification, use of standardized terminology, and proper documentation of findings are crucial for the integrated and appropriate management of these patients.
Disorders of Sex Development

Saving babies from mental retardation and death is the aim of the newborn screening program. A complex process of sample collection, processing and feedback is undertaken before reaching this goal. As with other systems, the newborn screening program is not perfect and periodic review is needed to continually improve services. Using maple syrup urine disease (which is the most common inborn error of metabolism detected through newborn screening) as an index case, this paper aims to present the gaps in diagnosis and management by citing cases and providing a commentary.
Maple Syrup Urine Disease ; Neonatal Screening

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.