Mutations in TTC19: expanding the molecular, clinical and biochemical phenotype

Koch, Johannes; Freisinger, Peter; Feichtinger, René G; Zimmermann, Franz A; Rauscher, Christian; Wagentristl, Hans P; Konstantopoulou, Vassiliki; Seidl, Rainer; Haack, Tobias B; Prokisch, Holger; Ahting, Uwe; Sperl, Wolfgang; Mayr, Johannes A; Maier, Esther M

doi:10.1186/s13023-015-0254-5

Orphanet Journal of Rare Diseases

Table 1 Clinical, biochemical, and molecular findings of the 4 patients with TTC19 deficiency

From: Mutations in TTC19: expanding the molecular, clinical and biochemical phenotype

		Patient 1 ^a	Patient 2 ^a	Patient 3 ^b	Patient 4 ^b
Sex		male	male	male	female
Ethnic origin		Turkish	Austrian	Romani	Romani
Age at onset of symptoms		neonatal	19 months	3 years	6 years
Signs/symptoms at onset		Lactic acidosis	Developmental delay, hypotonia, dysarthria, ataxia	Developmental delay, hypotonia, regression, ataxia	Mild developmental delay, hypotonia
Current clinical condition		10 years, alive, vegetative state, refractory epilepsy, bilateral spasticity	9 years, alive, bilateral spasticity, dystonia, wheelchair-bound, dysarthria, dysphagia	14 years, alive, wheelchair-bound, bilateral spasticity	7 years, motor skills delayed, normal schooling
*TTC19* mutations (homozygous) ^c		c.971T>C; p.Leu324Pro	c.656T>G; p.Leu219*^d	c.554T>C; p.Leu185Pro	c.554T>C; p.Leu185Pro
Muscle biopsy					not performed
MRC complex III activity	% of Lowest Control	28%	31%	normal
Absolute value (reference range)		0.40 (1.45-3.76)	0.45 (1.45-3.76)	1.49 (1.45-3.76)
Western blotting	TTC19	trace	trace	trace
	Complex III, core 1	normal	normal	normal
	Complex III, core 2	normal	normal	normal
	Complex III, Rieske	normal	normal	normal
Metabolic data
Elevated lactate (blood/CSF)		+ / n.a.	+ / n.a.	- / -	-
Neurological status
Ataxia		+	+	+	-
Dysphagia		+	+	+	-
Dysarthria		+	+	+	-
Dystonia		+	+	-	-
Enhanced tendon reflexes		+	+	+	+
Spasticity		+	+	+	-
Hypotonia		+	+	+	+
Symptomatic epilepsy		+	-	+	-
Regression/decline		+	+	+	-
Loss of speech		+	+	+	-
Neuroimaging features
Leigh syndrome		+	+	+	-
Hyperintensities (T2-weighted)	N. caudatus	+	+	+	+
	Putamen	+	+	+	+
	Medulla oblongata	+	+	+	-
	Mesencephalon	+	+	+	-
	Olivary nucleus	+	+	+	-
Leukoencephalopathy		+	+	n.a.	-
Cerebellar atrophy		+	+	+	(+)
Pontine atrophy		-	-	-	-
Cortical atrophy		+	+	+	-
¹H-MRS (lactate peak)		n.a	n.a	+	n.a.

Abbreviations are as follows: n.a., not available; MR, magnetic resonance; ¹HMRS, proton magnetic resonance spectroscopy; Enzyme activities were normalized to citrate synthase (CS). Absolute values and reference ranges are given in (mU/mU CS).
^aInvestigated by exome sequencing.
^bThese individuals are siblings.
^ccDNA (NM_017775);Protein (NP_060245).
^dMutation was previously published [1].

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ISSN: 1750-1172

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