INDIAN PEDIATRICS 499 VOLUME 54 __ JUNE 15, 2017 CASE R R R R REPORT An Indian Family with Tyrosine Hydroxylase Deficiency JYOTINDRA NARAYAN GOSWAMI, NAVEEN SANKHYAN AND PRATIBHA D SINGHI From Pediatric Neurology and Neurodevelopment Unit, Department of Pediatrics, Advanced Pediatrics Centre, PGIMER, Chandigarh, India. Background: Tyrosine Hydroxylase deficiency is a rare neurotransmitter disorder. Case Characteristics: An Indian family with the disorder. Observation: Phenotypic variation, elevated serum prolactin, genetic confirmation, and partial treatment-responsiveness. Messages: Tyrosine Hydroxylase deficiency is a treatable inborn error of metabolism and serum prolactin assists in diagnosis. Keywords: Segawa syndrome, Neurodegeneration, Neurotransmitter disorder. Correspondence to: Prof. Pratibha Singhi, APC, PGIMER, Chandigarh 160 012, India. doctorpratibhasinghi@gmail.com Received: September 06, 2016; Initial review: December 20, 2016; Accepted: March 28, 2017. T yrosine hydroxylase (TH) deficiency is an autosomal recessive neurotransmitter disorder that may have a heterogeneous presentation [1]. We report an Indian family with this rare disorder to sensitize pediatricians about the importance of clinical suspicion and serum prolactin in diagnosing this condition. We also wish to highlight its phenotypic variability and treatment-responsiveness. Case Report A 10-month-old boy presented with acute onset, rapidly progressive loss of milestones. The child was term born to non–consanguineous, healthy, Indian couple. His birth-weight was 2.8 kgs and perinatal period was uneventful. Pre-morbidly, he was developmentally normal. At nine months, the child had an episode of low-grade fever with rhinorrhea for four days. Subsequently, he became lethargic and rapidly lost abilities to sit, turn-over, reach for objects or babble. He continued to track visually and smile back. He had an episode of generalized seizure for five minutes on second day of illness. On examination he was well built, lethargic with generalized hypotonia and paucity of limb movements. He spontaneously recovered to normalize over three weeks. Two weeks later, he had an acute, unprovoked, rapid recurrence of milestone loss evolving over one week. At the nadir, he could not hold his neck or voluntarily reach out with his hands. He vocalized but could not coo. He recognized parents but lost stranger- anxiety. Parents felt that the child was flaccid and had difficulty swallowing solids. He did not have abnormal breathing, vomiting, abnormal eye/ limb movements, posturing, seizures, unconsciousness or abnormal urine odour. On repeat examination, the positive findings were significant generalized hypotonia and paucity of spontaneous limb movements. Child’s hematological and biochemical profile, arterial ammonia, serum biotinidase, homocysteine, creatine phosphokinase, anti-TPO antibody titers, cere- brospinal fluid study CSF study, electroencephalogram, nerve conduction study, electromyography, Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS) brain, Tandem Mass Spectroscopy (TMS), urinary organic acid profile by Gas Chromatography-Mass Spectroscopy (GC-MS) and serum aminoacidogram were unremarkable. He was managed empirically with carnitine, Coenzyme-Q, thiamine, riboflavin, folic acid besides physiotherapy, multisensory stimulation, and nutritional support. On follow up at two years of age, he had attained partial neck control, voluntary reach, babbling and stranger anxiety . He now was noticed to have intermittent dystonic upper- limb twisting which increased during crying and disappeared during sleep. While this child was being followed up, his younger sister was born and evaluated for being symptomatic. The younger six-month-old female sibling was term- born with uneventful perinatal period and was pre- morbidly developmentally normal. She was first noticed to have episodes of brief, paroxysmal, non-repetitive, abnormal, multi-directional eye movements at the age of three months. She did not have frothing, sweating, flushing, cyanosis, or pallor. Frequency of these episodes increased from once a day to about ten per day by one month. The child also developed feeding difficulty in the form of abnormal lip and tongue movements when milk was Copyright of Indian Pediatrics 2017 For personal use only. Not for bulk copying or unauthorized posting to listserv/websites