ORIGINAL ARTICLE A child with phenylketonuria and focal segmental glomerulosclerosis, the bright side of proteinuria Fatma Rabah 1 & Khalid Al-Thihli 2 & Mohamed El-Naggari 1 & Ibtisam B. Elnour 1 Received: 30 October 2016 /Accepted: 20 March 2017 # Springer Science+Business Media New York 2017 Abstract Phenylketonuria (PKU) is the most common inborn error of amino acid metabolism. Phenylalanine hydroxylase is the underlying deficient enzyme. If left untreated, growth fail- ure, microcephaly, global developmental delay, seizures and severe intellectual impairment would characterize the clinical picture of PKU. On the other side of protein homeostasis lies nephrotic syndrome. It is a well-known quantitative defect due to significant proteinuria. Focal segmental glomerulosclerosis (FSGS) is a special congenital variant affecting children and adults. Hereby, we describe a three- year old male child who presented with generalized edema and global developmental delay. Investigations revealed PKU along with FSGS. We as- sume that congenital nephrosis ameliorated the picture of PKU, and had a salutary effect on the growth and develop- ment. Such coexistence between PKU and FSGS hasn’t been described before. Keywords PKU . FSGS . NPHS2 . Oman . Metabolic . Brain development Abbreviations FSGS Focal segmental glomerulosclerosis Phe phenylalanine PKU Phenylketonuria Introduction Phenylketonuria (PKU) is the most prevalent inborn error of amino acid metabolism. Deficiency of phenylalanine hydrox- ylase enzyme is the offending cause of PKU, with resultant high serum phenylalanine (Phe) and low tyrosine levels (Blau et al. 2010). Such consequences are usually se- vere when PKU is left untreated. Serious mental dam- age with progressive intellectual impairment as well as au- tism, seizures, neurological motor deficits and eczematous rash would be the inevitable outcome. (Blau et al. 2010; Loeber 2007). Patients with classic PKU have Phe levels of more than 1200 umol/L exceeding 10-fold the level of normal subject (Blau et al. 2010). The prevalence of PKU in Europe is one case per 10.000 live births, (Loeber 2007). Being an autosomal recessive dis- order, high levels of consanguinity increase the prevalence. This is the case in Turkey where the prevalence of persistent hyperphenylalaninemia is about one in every 4000 births due to the high consanguinity (Ozalp et al. 2001) and founder effect (Zschocke 2003). Focal segmental glomerulosclerosis (FSGS) is the major cause of idiopathic steroid-resistant nephrotic syndrome in children and adults. The clinical hallmarks of FSGS include nephrotic syndrome and frequent progression to end-stage kidney disease (Dingli et al. 2005). Renal biopsy of FSGS is characterized by focal glomerulosclerosis or tuft col- lapse, segmental hyalinosis, occasionally IgM staining on immunofluorescence, and effacement of foot pro- cesses on electron microscopy. Mutations of NPHS2 gene, encoding for a podocyte protein podocin, are a common underlying molecular defect of congenital ne- phrotic syndrome as well as of steroid resistant ne- phrotic syndrome. NPHS2 gene is located on chromosome 1q25-q3 (Dingli et al. 2005). * Fatma Rabah fatmarabah@gmail.com 1 Child Health Department, Sultan Qaboos University Hospital, PO Box 38, Al-Khoud 123, Muscat, Oman 2 Genetics Department, Genetic and Developmental Medicine Clinic, Sultan Qaboos University Hospital, Muscat, Oman Metab Brain Dis DOI 10.1007/s11011-017-9998-z