Nonketotic Hyperglycinemia in Tunisia. Report upon a Series of 69 Patients

Fahmi Nasrallah; Sameh Hadj-Taieb; Amel Ben Chehida; Awatef Jelassi; Sana Ben Massoued; Manel Charfi; Wiem Zidi; Fethi Amri; Khaled Ben Helel; Houssain Mejaoual; Hassen Seboui; Nabiha Mahdhaoui; Abdellatif Gargouri; Kamel Monastiri; Ilhem Turki; Myriam Cheour; Haifa Sanhaji; Neji Tebib; Moncef Feki; Naziha Kaabachi

doi:10.1055/s-0040-1712489

Neuropediatrics, Inhaltsverzeichnis

Neuropediatrics 2020; 51(05): 349-353
DOI: 10.1055/s-0040-1712489

Original Article

Nonketotic Hyperglycinemia in Tunisia. Report upon a Series of 69 Patients

Fahmi Nasrallah

¹Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia

²Laboratory of Biochemistry, Rabta Hospital, Tunis, Tunisia

³Department of Pediatrics, Rabta Hospital, Tunis, Tunisia

,

Sameh Hadj-Taieb

¹Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia

²Laboratory of Biochemistry, Rabta Hospital, Tunis, Tunisia

,

Amel Ben Chehida

¹Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia

³Department of Pediatrics, Rabta Hospital, Tunis, Tunisia

,

Awatef Jelassi

¹Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia

²Laboratory of Biochemistry, Rabta Hospital, Tunis, Tunisia

,

Sana Ben Massoued

¹Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia

³Department of Pediatrics, Rabta Hospital, Tunis, Tunisia

,

Manel Charfi

⁴Department of Neonatology, Hedi Chaker Hospital, Sfax, Tunisia

,

Wiem Zidi

¹Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia

²Laboratory of Biochemistry, Rabta Hospital, Tunis, Tunisia

,

Fethi Amri

⁵Department of Pediatrics, Ibn Jazzar Hospital, Kairouan, Tunisia

,

Khaled Ben Helel

⁵Department of Pediatrics, Ibn Jazzar Hospital, Kairouan, Tunisia

,

Houssain Mejaoual

⁵Department of Pediatrics, Ibn Jazzar Hospital, Kairouan, Tunisia

,

Hassen Seboui

⁶Department of Neonatology, Farhat Hached Hospital, Sousse, Tunisia

,

Nabiha Mahdhaoui

⁶Department of Neonatology, Farhat Hached Hospital, Sousse, Tunisia

,

Abdellatif Gargouri

⁴Department of Neonatology, Hedi Chaker Hospital, Sfax, Tunisia

,

Kamel Monastiri

⁷Department of Neonatology, Fattouma Bourguiba Hospital, Monastir, Tunisia

,

Ilhem Turki

¹Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia

⁸Department of Child Neurology, National Institute of Neurology, Tunis, Tunisia

,

Myriam Cheour

¹Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia

⁹Department of Neonatology, Center of Maternity and Neonatology of Tunis, Tunis, Tunisia

,

Haifa Sanhaji

¹Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia

²Laboratory of Biochemistry, Rabta Hospital, Tunis, Tunisia

,

Neji Tebib

¹Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia

³Department of Pediatrics, Rabta Hospital, Tunis, Tunisia

,

Moncef Feki

¹Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia

²Laboratory of Biochemistry, Rabta Hospital, Tunis, Tunisia

,

Naziha Kaabachi

¹Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia

²Laboratory of Biochemistry, Rabta Hospital, Tunis, Tunisia

› Institutsangaben

Abstract

Aim The aim of the study is to report on epidemiological, clinical, and biochemical characteristics of nonketotic hyperglycinemia (NKH) in Tunisia.

Methods Patients diagnosed with NKH in Laboratory of Biochemistry at Rabta hospital (Tunis, Tunisia) between 1999 and 2018 were included. Plasma and cerebrospinal fluid (CSF) free amino acids were assessed by ion exchange chromatography. Diagnosis was based on family history, patient's clinical presentation and course, and increased CSF to plasma glycine ratio.

Results During 20 years, 69 patients were diagnosed with NKH, with 25 patients originating from Kairouan region. Estimated incidences were 1:55,641 in Tunisia and 1:9,684 in Kairouan. Consanguinity was found for 73.9% of the patients and 42% of the families have history of infantile death due to a disease of similar clinical course than the propositus. Clinical symptoms initiated within the first week of life in 75% of the patients and within the first 3 months in 95.7% ones. The phenotype was severe in 76.8% of the patients. Main symptoms were hypotonia, feeding difficulties, coma, apnea, and seizures. Most patients died within few days to months following diagnosis. CSF to plasma glycine ratio was increased in all patients. CSF and plasma glycine levels were negatively correlated with age of disease onset and severity.

Conclusion NKH is quite frequent in Tunisia. Kairouan region has the highest NKH incidence rate, worldwide. However, due to lack of confirmatory enzymatic and genetic tests, NKH diagnosis was based on first-line biochemical tests. Characterization of causal mutations is needed for accurate diagnosis and prenatal diagnosis of this devastating life-threatening disease.

Keywords

cerebrospinal fluid - incidence - glycine - nonketotic hyperglycinemia

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References
1 Hamosh Johnston MV. Nonketotic hyperglycinemia, In: Scriver CR, Beaudet AL, Sly WS, Valle D. , eds. The Metabolic and Molecular Bases of Inherited Disease, 11th ed. New York, NY: McGraw-Hill; 2001: 2065-2078
2 Rezvani Melvin JJ. Defects in metabolism of amino acids, In: Kliegman RM, Stanton BF, St GemeJ, Behrman RE. , eds. Nelson Textbook of Pediatrics. 19th ed.. Philadelphia, PA: Elsevier; 2011: 439-440
3 Van Hove JLK, Coughlin II C, Swanson M, Hennermann JB. Nonketotic hyperglycinemia. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A. , eds. Source Gene Reviews®. Seattle, WA: University of Washington, Seattle; 2002: 1993-2020
4 Coughlin II CR, Swanson MA, Kronquist K. , et al. The genetic basis of classic nonketotic hyperglycinemia due to mutations in GLDC and AMT. Genet Med 2017; 19 (01) 104-111
5 Khemir S, Tebib N, Nasrallah F. , et al. Phenylketonuria in Tunisian institutions for the mentally handicapped. Arch Dis Child 2009; 94 (08) 647-648
6 Hadj-Taieb S, Nasrallah F, Hammami MB. , et al. Aminoacidopathies and organic acidurias in Tunisia: a retrospective survey over 23 years. Tunis Med 2012; 90 (03) 258-261
7 Dinopoulos A, Matsubara Y, Kure S. Atypical variants of nonketotic hyperglycinemia. Mol Genet Metab 2005; 86 (1-2): 61-69
8 Hennermann JB, Berger JM, Grieben U, Scharer G, Van Hove JL. Prediction of long-term outcome in glycine encephalopathy: a clinical survey. J Inherit Metab Dis 2012; 35 (02) 253-261
9 Institut National de la Statistique. Available at: http://www.ins.tn/fr/statistiques . Accessed June 3, 2019
10 Veríssimo C, Garcia P, Simões M. , et al. Nonketotic hyperglycinemia: a cause of encephalopathy in children. J Child Neurol 2013; 28 (02) 251-254
11 von Wendt L, Hirvasniemi A, Similä S. Nonketotic hyperglycinemia. A genetic study of 13 Finnish families. Clin Genet 1979; 15 (05) 411-417
12 Applegarth DA, Toone JR, Lowry RB. Incidence of inborn errors of metabolism in British Columbia, 1969-1996. Pediatrics 2000; 105 (01) e10
13 Kure S, Rolland MO, Leisti J. , et al. Prenatal diagnosis of non-ketotic hyperglycinaemia: enzymatic diagnosis in 28 families and DNA diagnosis detecting prevalent Finnish and Israeli-Arab mutations. Prenat Diagn 1999; 19 (08) 717-720
14 Krawczak M, Barnes RH. How obedience of marriage rules may counteract genetic drift. J Community Genet 2010; 1 (01) 23-28
15 Santos S, da Silva Pequeno AA, Pessoa A. , et al. Increased prevalence of inherited neuromuscular disorders due to endogamy in Northeast Brazil: the need of community genetics services. J Community Genet 2014; 5 (03) 199-203
16 Swanson MA, Coughlin Jr CR, Scharer GH. , et al. Biochemical and molecular predictors for prognosis in nonketotic hyperglycinemia. Ann Neurol 2015; 78 (04) 606-618